Bipolar Disorder Research Articles

Valproate-induced hyperammonemic encephalopathy in neurosurgical patients: Our experience and systematic literature review.

Sodium valproate is used for the management of seizures, status epilepticus, chronic pain syndrome, bipolar, and other affective disorders. Even with an acceptable safety profile, severe idiosyncratic reactions can occur with valproate use. A rare, serious, and life-threatening side effect of valproate is valproate-induced hyperammonemic encephalopathy (VHE). We intend to analyze the clinical presentation, diagnosis, treatment options, and outcome of VHE in neurosurgical patients and review the pertinent literature on this rare sequelae. We retrospectively reviewed patients who developed VHE following valproate use, either for the treatment of epilepsy or for seizure prophylaxis in our centre. We analyzed the demographic details, clinical presentation, diagnosis, management, and outcomes. A total of four patients with a mean age of 26.3 ± 5.1 (range 19 - 32years). Valproate was prescribed for primary seizure prophylaxis in 2 patients (50%). The commonest etiology for valproate prescription was for brain tumors (3, 75%) followed by drug-refractory epilepsy (DRE) (1, 25%). None of the patients were documented to have urea cycle disorder. The mean daily prescribed dosage of valproate was 1250 ± 559mg and the mean duration of administration was 13 ± 13.3months (range 4months - 36months). The mean serum NH3 level was 136,5 ± 44.2µmol/L (range 107 - 212.8) and all patients (4, 100%) had hyperammonemia with a mortality rate of 50% (2 patients). The hyperammonemia was treated by stopping the valproate use (4, 100%) and dialysis (2, 50%). Normalization of ammonia levels led to clinical improvement in 50% (2 patients). Neurological deterioration in the postoperative period is a diagnostic challenge. VHE is a rare and life-threatening sequelae of Valproate-associated Hyperammonemia (VAH) in neurosurgical patients. A high index of suspicion is required due to its ambiguous presentation. Early diagnosis and prompt treatment can change the course of this life-threatening sequelae.

Diseases Caused by and Behaviors Associated with Toxoplasma gondii Infection

Toxoplasma gondii is an Apicomplexan parasite that is estimated to infect at least one-third of the global human population. T. gondii infection may be transmitted horizontally or vertically. The main risk factors for transmission to humans are related to diet, especially the consumption of undercooked meat, along with soil contact. In immunocompetent persons, the acute infection may go undetected as it typically produces minor, non-specific symptoms that are self-limited. After infection is established, recurrent retinochoroiditis is the most common clinical disease. In contrast, severe systemic or cerebral toxoplasmosis may be life-threatening for immunocompromised individuals. Furthermore, congenital toxoplasmosis acquired in utero may have devastating consequences if not recognized and promptly treated. A growing body of research has identified associations between latent T. gondii infection, and personality traits and risk-taking behaviors. Other studies have documented associations between latent infection and psychiatric conditions that include schizophrenia and bipolar affective disorder. With no current treatment regimens being curative of T. gondii infection, effective prevention measures at both the public health and individual levels are vitally important.

White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals.

Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal stratum. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.

The gut microbiota-brain connection: insights into major depressive disorder and bipolar disorder

Major depressive disorder (MDD) and bipolar disorder (BD) are two of the most prevalent mood disorders that seriously jeopardize both physical and mental health. The current diagnosis of MDD and BD relies primarily on clinical symptoms. However, correctly differentiating between MDD and BD during depressive episode states remains a substantial clinical challenge. The human gut hosts a large and diverse microbiota, which plays a pivotal role in various physiological processes. Emerging evidence suggests that the gut microbiota (GM) exerts beneficial effects on mental health disorders, including MDD, BD, and schizophrenia, through the microbe-gut-brain axis (MGBA). In recent years, the relationship between GM and mood disorders has garnered considerable attention, leading to intensive research in this area. The MGBA is a bidirectional communication system between the gut and the brain. Growing evidence indicates that the brain can influence the GM, which in turn may modulate the brain through this axis. This review aims to explore the changes in the GM of patients with MDD and BD and evaluate the effects of different treatments on their GM, including medication, probiotic, prebiotic and synbiotic interventions, and fecal microbiota transplantation (FMT). By doing so, we seek to identify potential disease-specific biomarkers, improve differential diagnosis, and offer novel therapeutic avenues for these disorders.

Factors affecting negative and positive emotions among spouses caring for patients with psychotic or bipolar disorder.

Spouses experience conflicting emotions when caring for partners with severe mental illnesses. They can have negative emotions while also regarding caregiving as positive and may develop a better marital relationship through the caregiving process. This study investigated factors affecting the negative and positive emotions of husbands and wives acting as caregivers of their spouses with severe mental illnesses. An online nationwide survey of 166 spouses caring for partners diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder was conducted. Caregivers' negative and positive emotions, personal and role strains in the care burden, sense of coherence, and patients' disabilities in family communication were assessed. We conducted a series of hierarchical multiple regression analyses to evaluate the effects of these factors on the emotions of husbands and wives separately. Among the 166 spouses, 112 (67%) were husbands and 54 (33%) were wives. Husbands were caregivers to 1.4 times as many individuals diagnosed with psychotic disorder as were wives. The negative emotions of husbands were linked to personal strain, whereas those of wives were associated with patient disability in family communication. Sense of coherence was the only factor predicting positive emotions for both sexes. Support for spousal caregivers should be adjusted according to sex. A reduction in husbands' personal strain can alleviate their negative emotions, whereas wives' negative emotions can be relieved by improving communication within their families. Regardless of sex, a higher sense of coherence level has the potential to suppress negative emotions and enhance positive emotions.

Temperament and creativity – implications for mental health and education

Creativity is a complex phenomenon, which level is affected by variables such as intellectual competence, temperament, personality and emotions. Research shows that patients with bipolar affective disorder have a higher level of creativity than healthy controls. The model of affective temperament developed by Hagop Akiskal enables the research on relationships between predispositions to bipolar disorder and creativity. Previous studies on the relationship between affective temperament and creativity are conducted by comparing temperaments of representatives of creative professions and people outside this group, as well as by studying the relationship between affective temperament and creativity assessed both subjectively and through objective tests. However, the temperamental traits contributing to creative potential have their downside, as they have been linked to higher risk of psychological and emotional problems. They may also be related to poorer educational and academic achievement. The article presents up to date research on the relationship between affective temperament and creativity, as well as mechanisms explaining them. It also discusses the relationship between temperament, mental health, and educational achievement, as well as its implications for psychological and pedagogical interventions.

Assessing the contributions of gender, clinical symptoms, and psychometric traits to non-suicidal self-injury behaviors in Chinese adolescents: a nomogram approach.

Non-suicidal self-injury (NSSI) behaviors among adolescents with mood disorders represent a significant global public health concern. This study aimed to assess the prevalence and identify key predictors of NSSI behaviors in Chinese adolescents diagnosed with depressive or bipolar disorders, addressing a critical gap in the literature. Data from 2343 participants in the Chinese Adolescent Depression Cohort (CADC) were analyzed. The study employed a comprehensive approach, utilizing medical records, clinical assessments, and validated psychometric instruments. Statistical analyses included chi-square tests, logistic regression, and ROC curve analyses, culminating in the development of a predictive nomogram. The prevalence of NSSI behaviors was strikingly high at 73.32%. Significant predictors included female gender (AOR = 2.14, 95% CI [1.70, 2.68]), presence of hallucinations (AOR = 1.52, 95% CI [1.18, 1.97]), borderline personality features (AOR = 1.03, 95% CI [1.01, 1.08]), and childhood trauma (AOR = 1.02, 95% CI [1.01, 1.03]). The study's key contribution is a predictive nomogram with an AUC of 0.74, demonstrating good efficacy in predicting NSSI behaviors. This research reveals an alarmingly high prevalence of NSSI behaviors in Chinese adolescents with mood disorders and identifies critical predictors spanning demographic, clinical, and psychometric domains. The developed nomogram offers a novel approach for risk assessment, highlighting the importance of comprehensive evaluations in adolescent mental healthcare. These findings have significant implications for developing targeted interventions and improving risk assessment strategies in clinical practice.

Optimizing Chronotherapy in Psychiatric Care: The Impact of Circadian Rhythms on Medication Timing and Efficacy

In many medical settings, medications are typically administered in the morning or evening, aligning with patients’ daily routines. This practice does not stem from chronotherapy, which involves scheduling drug administration to enhance its effectiveness, but rather from the way clinical operations are structured. The timing of drug administration can significantly affect a medication’s effectiveness and side effects, with the impact varying by up to ten times based on circadian rhythms. Disorders such as major depression, bipolar disorder, and schizophrenia are linked to disruptions in these rhythms. Recent studies have found that circadian dysfunctions, including genetic and neurohumoral changes, underlie many psychiatric conditions. Issues such as an altered glucocorticoid rhythm due to impaired HPA axis function, disturbed melatonin balance, and sleep disturbances have been noted in psychotic disorders. Furthermore, mood disorders have been associated with changes in the expression of circadian rhythm genes such as Clock, Bmal1, and Per. Considering that the absorption, biodistribution, effects on target organs, half-life, metabolism, and elimination of drugs are all influenced by the body’s circadian rhythms, this narrative review explores the optimal timing of medication administration to maximize efficacy and minimize side effects in the treatment of psychiatric disorders. By closely monitoring circadian variations in cortisol, melatonin, and key clock genes, as well as by deepening our understanding of the metabolisms and pharmacokinetics of antipsychotic medications, we propose a chronotherapy approach for psychiatric patients that could significantly enhance patient care.

Australian community and inpatient general public sector mental health services between 2017-18 and 2021-22: Relative stasis in bed capacity, increasing outpatient demand, and stunted expenditure.

To descriptively analyse Australian public sector General Mental Health Services (GMHS) expenditure, ambulatory, and inpatient services, including key performance indicators (KPIs) in comparison with other subspeciality mental health services (MHS). We descriptively analysed data published by the Australian Institute of Health and Welfare (AIHW), including inpatient, ambulatory services, expenditure, and KPIs. From 2017-18 to 2021-22, per capita expenditure for Australian GMHS (18-64) rose by an average annual inflation-adjusted change of 2%. Overall bed numbers remained static, with non-acute beds declining, and commensurate expansion of acute beds. Community GMHS had high outpatient utilisation, with high rates of schizophrenia, schizoaffective disorder, and bipolar affective disorders as primary diagnoses in mid-life. From 2017-18 to 2021-22, GMHS inpatient and ambulatory episodes had decreasing rates of significant improvement and increasing rates of significant deterioration. Although GMHS has the highest overall population and service utilisation, there has been static bed availability and relatively small increases in expenditure which are occurring concurrently with worsening clinical outcomes. Evidence-based modelling of GMHS and outcomes is required to inform future service improvement.

Corrigendum: Aberrant functional connectivity of sensorimotor network and its relationship with executive dysfunction in bipolar disorder type I

Corrigendum: Aberrant functional connectivity of sensorimotor network and its relationship with executive dysfunction in bipolar disorder type I

The critical intersection of mental health and oral health in severe mental disorders.

To highlight the critical need for integrated healthcare approaches for individuals with severe mental disorders and poor oral health. Review and discussion of factors contributing to elevated DMFT (decayed, missing, and filled primary teeth) indices in individuals with severe mental disorders. Higher DMFT indices are reported in individuals with schizophrenia and bipolar disorder due to medication side effects, cognitive impairments, and socio-economic challenges. Emphasis on the necessity of combining mental and dental health services through regular dental check-ups, specialized education programs, and professional collaboration. Integrated healthcare strategies are essential to improve overall patient care and well-being for those with severe mental disorders.

Recurrent catatonia in a patient with bipolar disorder and polycythemia: A case report

We report the diagnostic and management challenges encountered in a case of a 57-year-old male patient with bipolar I disorder and comorbid polycythemia secondary to obstructive sleep apnea, who was treated in our inpatient psychiatric unit for suicidal ideation and recurrent catatonia. He was found to have catatonia with a Bush–Francis Catatonia Rating Scale score of 18. He subsequently exhibited a positive response to the lorazepam challenge test. Before discharge, his daily lorazepam dose was titrated to 6 mg, which led to resolution of catatonic symptoms, and was tapered to discontinuation. During the second hospitalization, the patient’s catatonia returned, but due to lorazepam-induced bradycardia, he refrained from taking more than 1 mg of the medication. Divalproex sodium and memantine were initiated as off-label catatonic treatment plus lurasidone for bipolar depression. The patient was also found to have a positive antinuclear antibody titer (1:160). The hemato-immunological abnormalities present in our patient complicated his catatonic condition, underscoring the need to explore medical and neuropsychiatric catatonic factors for accurate diagnosis of this neuropsychiatric syndrome.

25 years into research with the Méhes Scale, a comprehensive scale of modern dysmorphology

It has been recognized that subtle, cosmetically insignificant anomalies tend to occur cumulatively in diseases with neurodevelopmental origin. These visible signs of morphogenesis errors are called minor physical anomalies (MPAs), serving as sensitive external markers of abnormal neurodevelopment. After the introduction of the Waldrop Scale, the studies conducted on MPAs in diseases with neurodevelopmental origin gave conflicting results. It has been debated that this discrepancy can be – at least partly – attributed to the use of the Waldrop Scale. Understanding the need of a comprehensive scale of MPAs that also differentiates according to the time of development, Hungarian pediatrician professor of University of Pécs, Károly Méhes developed a scale with 57 items, the only scale differentiating minor malformations from phenogenetic variants. With the use of the Méhes Scale, our research group has been investigating the role of abnormal neurodevelopment in different neuropsychiatric and neurologic disorders since 1997. 25 years into our research, in this review we summarize the results of our 18 research articles on MPAs in different diseases. We have found an increased number of MPAs, especially in the head and mouth region, in patients with schizophrenia, bipolar disorder, Tourette syndrome, autism and many epilepsy syndromes, fortifying the role of abnormal neurodevelopment in these diseases. Moreover, an increased number of MPAs was detected among the first-degree relatives of patients with schizophrenia and bipolar I disorder, supporting the hypothesis about MPAs being endophenotypic trait markers.

General health and social outcomes 50 years after exposure to antenatal betamethasone: follow-up of a randomised controlled trial

BackgroundAntenatal corticosteroids are recommended for women at risk of preterm birth from 24 to 34 weeks’ gestation as they reduce neonatal morbidity and mortality, but evidence regarding their long-term effects on offspring is limited. This study assessed general health and social outcomes 50 years after antenatal exposure to corticosteroids.MethodsWe assessed 424 adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. The first 717 mothers received two intramuscular injections of betamethasone (6 mg betamethasone sodium phosphate and 6 mg betamethasone acetate) or placebo given 24 h apart and the subsequent 398 received two injections of double dose betamethasone (12 mg betamethasone sodium phosphate and 12 mg betamethasone acetate) or equivalent volume of placebo. Follow-up included a health questionnaire and consent for access to administrative data sources. Outcome categories included mental health (depression, anxiety, bipolar affective disorder, schizophrenia and treatment or hospital admission for any mental health disorder), general health (chronic kidney disease, cancer diagnosis, bone fracture, oral health, allergies, functional difficulties and physical activity) and social outcomes (educational attainment, employment and criminal convictions). Investigators remained blinded to treatment allocation. Analyses were adjusted for gestational age at entry, sex and clustering.ResultsWe assessed 424 adult offspring (46% of survivors; mean [SD] age 49.3 [1.0] years; 212 [50%] female). There was no difference in mental health, general health and social outcomes between those exposed to betamethasone and those exposed to placebo, with the exception that osteoporotic site fracture in adulthood was more likely to have occurred in the betamethasone group compared with placebo (adjusted relative risk 1.57, 95% CI 1.00, 2.48, p = 0.05). No dose–effect relationship was evident and there was no difference in the proportion with at least one fracture. Follow-up rate and lack of in-person assessments were the main limitations.ConclusionsThere is no evidence that antenatal corticosteroids have clinically important effects on general health and social outcomes up to 50 years of age.

Early diagnosis of nonconvulsive status epilepticus due to lithium intoxication using 6-channel electroencephalography.

Nonconvulsive status epilepticus is a severe complication of lithium intoxication that requires prompt diagnosis and treatment. While conventional electroencephalography (EEG) remains the gold standard for diagnosis for nonconvulsive status epilepticus, its implementation in emergency settings can be challenging and time-consuming. We present a case in which simplified EEG with six electrodes enabled rapid detection and monitoring of nonconvulsive status epilepticus in lithium intoxication in the emergency setting. A 65-year-old woman with stable bipolar disorder presented to our emergency department with impaired consciousness. She had been maintained on lithium carbonate (1600mg daily) and carbamazepine (400mg daily) for over 10 years. Following two weeks of nausea and recent onset of agitation and slurred speech, she developed generalized convulsions. Laboratory examinations revealed elevated serum lithium (3.88 mEq/L) and acute renal dysfunction (creatinine 347.5μmol/L). After resolving initial convulsions, a simplified sixelectrode EEG (Neurofax EEG-1250, Nihon Kohden Corporation, Tokyo, Japan), applied by an emergency physician, demonstrated generalized spike and wave patterns consistent with nonconvulsive status epilepticus. Despite initial seizure control with midazolam during intubation, continuous EEG monitoring revealed recurrent nonconvulsive status epilepticus. After hemodialysis and continued deep sedation, she was discharged on day 40 without neurological sequelae. This case demonstrates the utility of simplified EEG in emergency settings for early detection and monitoring of nonconvulsive status epilepticus in lithium intoxication. The ability of emergency physicians to apply and interpret simplified EEG enabled timely intervention and prevention of neurological complications. While further research is needed to validate interpretation protocols by non-EEG specialists, simplified EEG shows promise as an accessible tool for rapid assessment of neurotoxicity in lithium intoxication, potentially improving patient outcomes through earlier intervention.

A transdiagnostic approach of negative symptoms in psychiatric disorders: replication of a two-factor structure in major depressive disorder and bipolar disorder.

Recent empirical findings suggest that negative symptoms are not limited to schizophrenia (SCZ) but also present in major depressive disorder (MDD) and bipolar disorder (BD) patients. Although SCZ patients generally showed a latent structure comprising the motivation and pleasure (MAP) and expression (EXP) factors, it remains unclear whether the same latent structure exists in MDD and BD patients. We administered the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS) to 179 MDD patients and 152 BD patients. Confirmatory Factor Analysis (CFA) was conducted to examine the one-factor model, the two-factor model of the MAP and the EXP domain, the five-factor model of anhedonia, avolition, asociality, alogia, and blunted affect, and the hierarchical model comprising the first-order five-factor, and the second-order two-factor (MAP and EXP factors). We further examined the correlations between demographics and the negative symptom dimensions found in the best factor model. The CFA showed that, when the CAINS and the BNSS were combined together, the two-factor model of MAP and EXP provided the best model fit than other competing models, in the MDD alone sample, BD alone sample, and the combined clinical sample. The two-factor model of the MAP and EXP appears to be a stable, transdiagnostic latent structure of negative symptoms across BD and MDD. Clarifying negative symptoms in MDD and BD can facilitate future research on the underlying neural mechanisms of the MAP and EXP dimensions.

Premature mortality and disparities in kidney healthcare for people with chronic kidney disease and severe mental health difficulties.

People with severe mental health difficulties, including schizophrenia, bipolar disorder and psychosis, have higher risk of chronic kidney disease (CKD). Little was known regarding clinical outcomes and utilisation of kidney care for people with CKD and severe mental health difficulties. We conducted a retrospective cohort analysis of individuals with CKD attending a tertiary renal unit in London, between 2006 and 2019. Individuals with severe mental health difficulty diagnoses were identified, and differences between those with and without severe mental health difficulties were analysed. Of the 5105 individuals with CKD, 112 (2.2%) had a recorded severe mental health difficulty diagnosis. The mean lifespan of those with severe mental health difficulties was 13.1 years shorter than those without severe mental health difficulties, t(1269) = 5.752, p < 0.001. People with severe mental health difficulties had more advanced CKD at their first nephrology appointment. There were no statistically significant differences between groups in the rates of kidney failure, age at onset of kidney failure, or time elapsed between first appointment and death/kidney failure. The number of inpatient admissions was similar between groups, but those with severe mental health difficulties had higher rates of emergency and ICU admissions. Among individuals on renal replacement therapy (RRT), those with severe mental health difficulties were less likely to receive a kidney transplant and peritoneal dialysis. For patients receiving haemodialysis, those with severe mental health difficulties had a higher proportion of shortened sessions, greater mean weight loss during sessions, and a higher proportion of serum potassium and phosphate levels outside normal ranges. Findings illustratea number of disparities in kidney healthcare betweenpeople with and without severe mental health difficulties, underscoring the need for interventions which prevent premature mortality and improve kidney care for this population.

Atlas of gray matter volume differences across psychiatric conditions: A systematic review with a novel meta-analysis that considers co-occurring disorders

Regional gray matter volume (GMV) differences between individuals with mental disorders and comparison subjects may be confounded by co-occurring disorders. To disentangle the disorder-specific GMV correlates, we conducted a large-scale multi-disorder meta-analysis using a novel approach that explicitly models co-occurring disorders. We systematically reviewed voxel-based morphometry studies indexed in PubMed and Scopus up to January 2023 comparing adults with major mental disorders (anorexia nervosa, schizophrenia-spectrum, anxiety, bipolar, major depressive, obsessive-compulsive, and post-traumatic stress disorders, plus attention-deficit/hyperactivity, autism spectrum, and borderline personality disorders) to comparison subjects. Two authors independently extracted data and assessed quality using the Newcastle-Ottawa Scale. We derived GMV correlates for each disorder using: a) a multi-disorder meta-analysis accounting for all co-occurring mental disorders simultaneously; b) separate standard meta-analyses for each disorder ignoring co-occurring disorders. We assessed the alterations' extent, intensity (effect size), and specificity (inter-disorder correlations and transdiagnostic alterations) for both approaches. We included 433 studies (499 datasets) involving 19,718 patients and 16,441 comparison subjects (51% females, aged 20-67 years). We provide GMV correlate maps for each disorder using both approaches. The novel approach, which accounted for co-occurring disorders, produced GMV correlates that were more focal and disorder-specific (less correlated across disorders and fewer transdiagnostic abnormalities). This work offers the most comprehensive atlas of GMV correlates across major mental disorders. Modeling co-occurring disorders yielded more specific correlates, supporting this approach's validity. The atlas NIfTI maps are available online.

Efficacy and Safety of Lumateperone for Bipolar Depression and Schizophrenia: A Systematic Review and Meta-Analysis.

This study aimed to evaluate the efficacy and safety of lumateperone in treating bipolar disorder and schizophrenia. A comprehensive literature search was conducted across multiple databases and websites from inception to July 16, 2024, to identify both published and unpublished randomized controlled trials (RCTs). Meta-analyses were performed using random-effects or fixed-effects models depending on statistical heterogeneity. Relative risks (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to summarize the effects. Out of 931 records screened, seven RCTs (four focusing on bipolar depression and three on schizophrenia) were eligible for inclusion. Lumateperone was efficacious in reducing depressive symptoms in bipolar depression (SMDs = -0.36, 95% CI: -0.59 to -0.13). In treating schizophrenia, lumateperone exhibited a lower combined SMD of -0.14 (95% CI: -0.27 to 0, P = 0.051, I² = 49.6%), showing no significant difference from the placebo group, although the p-value approached significance. The lumateperone group showed significantly higher response rates compared to placebo in both bipolar depression (RRs = 1.27, 95% CI: 1.07 to 1.51) and schizophrenia (RRs = 1.44, 95% CI: 1.12 to 1.86). Common treatment-emergent adverse events included somnolence, dry mouth, dizziness, nausea, and headache (RRs = 1.30 to 3.29). Importantly, lumateperone did not significantly increase extrapyramidal symptoms (EPS, RRs = 1.46, 95% CI: 0.84 to 2.53). Lumateperone is effective in treating bipolar depression but does not significantly reduce symptom severity in schizophrenia. It has a favorable safety and tolerability profile. However, caution is warranted in interpreting these findings due to the limited number of studies included.

Risk of subsequent Parkinson's disease among patients with bipolar disorder or major depression: A nationwide longitudinal study in Taiwan.

Bipolar disorder (BD) and major depression have been associated with an increased risk of developing Parkinson's disease (PD); however, few studies have directly compared the risk of PD development between patients with BD and major depression while considering relevant risk factors and psychotropic medications. Using the Taiwan National Health Insurance Research Database, 21,186 patients with BD, 21,188 patients with major depression, and 42,374 controls were enrolled between 2001 and 2009, and followed until the end of 2011. Individuals who developed PD during the follow-up period were identified. Cox regression models were used to analyze the hazard ratio (HR) of developing PD, adjusting for demographic factors, comorbidities, and psychotropic medication usage. Both patients with BD [HR 8.63, 95% confidence interval (CI) 6.35-11.72] and those with major depression (HR 5.68, 95% CI 4.15-7.78) had an elevated risk of subsequent PD compared to the controls. Patients with BD were associated with a 51% increased risk of subsequent PD compared with patients with major depression. Long-term treatment with antiepileptic mood stabilizers was associated with increased PD risk among patients with late-onset BD and high Charlson comorbidity index scores. Lithium was not associated with an increased PD risk. The study highlights an elevated PD risk in patients with BD and major depression compared to the controls, with BD patients at highest risk. Further research is needed to elucidate the complex interplay between psychotropic medications and neurodegenerative processes in BD, aiming to optimize therapeutic strategies and improve patient outcomes.